During the past several years, we have been studying the regulation of protein synthesis in normal, toxically injured, and diseased liver in model systems derived from rats. Our most recent studies have been directed toward the isolation and characterization of albumin mRNA and we have developed molecular hybridization technology to study albumin mRNA biogenesis and function. We have measured subcellular distribution of albumin mRNA in the cytoplasm of normal liver and find that 97-98% of albumin mRNA sequences are located in membrane-bound polyribosomes to mRNPs free in the cytosol. This is accompanied by a marked depression in albumin synthesis. When rats are refed a mixture of 20 amino acids, albumin mRNA distribution returns to normal in 1 hour. The response to tryptophan refeeding is more sluggish with movement of albumin mRNa into free monosomes in 1 hour and membrane-bound polysomes. Using molecular hybridization technology, we have also begun to examine nuclear events in albumin mRNA biogenesis and have determined that albumin mRNA is synthesized as a higher molecular weight precursor in the nucleus. Presently, we are trying to clone albumin cDNA in E. coli to further our studies of albumin gene regulation.